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Here, we conducted continuous longitudinal analyses starting at baseline of prime vaccination until 3–4 months after boost on a single epitope level, to track the trajectories of bnt162b2 vaccine-elicited spike-specific CD8 + T cell responses in comparison to spike-specific CD4 + T cells, B cells, antibodies and their neutralizing activity. Previous studies focused on the analysis of the overall vaccine-elicited spike-reactive T cell response 4, 5, 7, 8, 12 however, by this approach, the strength, dynamics and functional capacity are underestimated or even blurred in contrast to analyses performed at the single epitope level 5.
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These observations point towards a key role of vaccine-induced T cells in early protection after prime vaccination. During this early phase, T cells and spike-specific antibodies are detectable 7, 8, whereas neutralizing antibodies first appear after boost 4, 5, 6, 10, 11.
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The onset of mRNA vaccine-mediated protection has been observed as early as 10–12 days after the first dose 3. Initial data revealed that all arms of adaptive immunity such as neutralizing antibodies, virus-specific CD4 + T cells with T helper 1 (T H1) polarization and IFNγ-producing CD8 + T cells emerge after prime or boost vaccination 4, 5, 9. The current SARS-CoV-2 vaccination campaign provides the unique opportunity to gain important insights into human CD8 + T cell biology in the context of prime or boost mRNA vaccination. Our results indicate that CD8 + T cells are important effector cells, are expanded in the early protection window after prime vaccination, precede maturation of other effector arms of vaccine-induced immunity and are stably maintained after boost vaccination. Compared with natural infection, vaccine-induced early memory T cells exhibited similar functional capacities but a different subset distribution.
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Boost vaccination induced a robust expansion that generated highly differentiated effector CD8 + T cells however, neither the functional capacity nor the memory precursor T cell pool was affected. Here we show on a single-epitope level that a stable and fully functional CD8 + T cell response is vigorously mobilized one week after prime vaccination with bnt162b2, when circulating CD4 + T cells and neutralizing antibodies are still weakly detectable. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. Vaccine-induced CD8 + T cells may therefore be the main mediators of protection at this early stage 7, 8. SARS-CoV-2 spike mRNA vaccines 1, 2, 3 mediate protection from severe disease as early as ten days after prime vaccination 3, when neutralizing antibodies are hardly detectable 4, 5, 6. Nature volume 597, pages 268–273 ( 2021) Cite this article Rapid and stable mobilization of CD8 + T cells by SARS-CoV-2 mRNA vaccine